The Blood–Brain Barrier in Psychoneuroimmunology

Geriatrics Research Education and Clinical Center, Veterans Affairs Medical Center-St. Louis, 915 North Grand Boulevard, St. Louis, MO 63106, USA.
Immunology and allergy clinics of North America (Impact Factor: 1.82). 06/2009; 29(2):223-8. DOI: 10.1016/j.iac.2009.02.001
Source: PubMed


The term ''psychoneuroimmunology'' connotes separate compartments that interact. The blood-brain barrier (BBB) is both the dividing line, physical and physiologic, between the immune system and the central nervous system (CNS) and the locale for interaction. The BBB restricts unregulated mixing of immune substances in the blood with those in the CNS, directly transports neuroimmune-active substances between the blood and CNS, and itself secretes neuroimmune substances. These normal functions of the BBB can be altered by neuroimmune events. As such, the BBB is an important conduit in the communication between the immune system and the CNS.

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    • "Although the CNS is isolated from the peripheral immune system by the blood–brain barrier (BBB), it is possible for cytokines to invade the CNS under normal physiological conditions (Banks, 2005). For example, activated maternal pro-inflammatory cytokines such as IL-1β, TNF-α, and IL-6 can invade the fetal CNS through various pathways (Banks, 2006). The possible mechanisms by which cytokines cross the BBB are saturable transport (Banks et al., 1989; Osburg et al., 2002), disruption of the BBB (Quagliarello et al., 1991), and through circumventricular organs that lack the BBB (Buller, 2001). "
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    ABSTRACT: Schizophrenia is a serious mental illness with chronic symptoms and significant impairment in psychosocial functioning. Although novel antipsychotics have been developed, the negative and cognitive symptoms of schizophrenia are still unresponsive to pharmacotherapy. The high level of social impairment and a chronic deteriorating course suggest that schizophrenia likely has neurodegenerative characteristics. Inflammatory markers such as pro-inflammatory cytokines are well-known etiological factors for psychiatric disorders, including schizophrenia. Inflammation in the central nervous systemis closely related to neurodegeneration. In addition to pro-inflammatory cytokines, microglia also play an important role in the inflammatory process in the CNS. Uncontrolled activity of pro-inflammatory cytokines and microglia can induce schizophrenia in tandem with genetic vulnerability and glutamatergic neurotransmitters. Several studies have investigated the possible effects of antipsychotics on inflammation and neurogenesis. Additionally, anti-inflammatory adjuvant therapy has been under investigation as a treatment option for schizophrenia. Further studies should consider the confounding effects of systemic factors such as metabolic syndrome and smoking. In addition, the unique mechanisms by which pro-inflammatory cytokines are involved in the etiopathology of schizophrenia should be investigated. In this article, we aimed to review(1) major findings regarding neuroinflammation and pro-inflammatory cytokine alterations in schizophrenia, (2) interactions between neuroinflammation and neurogenesis as possible neural substrates for schizophrenia, and (3) novel pharmacological approaches.
    Progress in Neuro-Psychopharmacology and Biological Psychiatry 06/2015; DOI:10.1016/j.pnpbp.2015.06.008 · 3.69 Impact Factor
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    • "Based on the possibility that peripheral cytokines can move into the CNS via the blood brain-barrier (BBB) (Banks, 2006), many studies have measured peripheral cytokine levels as indirect "
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    ABSTRACT: BACKGROUND: Despite the substantial role of the cytokine network in depression and suicide, few studies have investigated the role of genetic polymorphisms of pro- and anti-inflammatory cytokines in suicide in major depressive disorder (MDD). The aim of this study was to investigate whether tumor necrosis factor-alpha (TNF-alpha) -308G>A, interferon-gamma (IFN-gamma) +874A>T, and interleukin-10 retain-->(IL-10) -1082A>G are associated with increased risk for suicide attempts in MDD. METHODS: Among patients with MDD, 204 patients who had attempted suicide and 97 control patients who had not attempted suicide were recruited. A chi-square test was used to identify a possible risk genotype or allele type for suicide. A subsequent multivariate logistic regression analysis was conducted to investigate the influence of a risk genotype or allele type adjusted for other environmental factors. retain-->The lethality of the suicide attempt was also tested between genotype and allele types among suicidal patients with MDD. RESULTS: The GG genotype of the TNF-alpha -308G>A polymorphism was found to significantly increase risk for suicide attempt (adjusted OR=2.630, 95% CI=1.206 to 5.734). IFN-gamma +874A>T and IL-10 -1082A>G were not associated with risk for suicide. Lethality of the suicide attempt was not associated with any of the three cytokine genotypes or allele types. LIMITATIONS: Limitations include a relatively small sample size and a cross-sectional design. CONCLUSIONS: TNF-alpha -308G>A polymorphism is an independent risk factor for suicide attempts in MDD. Future studies should clarify the neural mechanisms by which the GG genotype of TNF-alpha -308G>A influences suicide in MDD.
    Journal of Affective Disorders 04/2013; 150(2). DOI:10.1016/j.jad.2013.03.019 · 3.38 Impact Factor
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    • "However, we also cannot rule out the possibility that IL- 10 entered the peripheral bloodstream from the cerebrospinal fluid, where it could have affected IL-6. Characteristically, inflammatory processes increase adhesion molecule expression, allowing cytokine leakage between CNS and periphery due to increased blood–brain barrier permeability (Banks, 2006; Dantzer, 2009; Elmquist et al., 1997). Notably, microgram levels of systemic IL- 10 have previously been used to ablate fever response in LPS treated rats (Cartmell et al., 2003), therefore it appears less likely that the ng levels of IL-10 administered i.c.v in these studies had their effects systemically. "
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    ABSTRACT: Postnatal maternal separation in rats causes a reduction of GABAergic parvalbumin-containing interneurons in the prefrontal cortex that first occurs in adolescence. This parvalbumin loss can be prevented by pre-adolescent treatment with a non-steroidal anti-inflammatory drug that also protects against excitotoxicity. Therefore, the neuropsychiatric disorders associated with early life adversity and interneuron dysfunction may involve neuroinflammatory processes and/or aberrant glutamatergic activity. Here, we aimed to determine whether delayed parvalbumin loss after maternal separation was due to inflammatory activity, and whether central administration of the anti-inflammatory cytokine interleukin (IL)-10 could protect against such loss. We also investigated the effects of maternal separation and IL-10 treatment on cortical NMDA receptor expression. Male rat pups were isolated for 4h/day between postnatal days 2-20. IL-10 was administered intracerebroventricularly through an indwelling cannula between P30-38. Adolescent prefrontal cortices were analyzed using Western blotting and immunohistochemistry for parvalbumin and NMDA NR2A subunit expression. We demonstrate that central IL-10 administration during pre-adolescence protects maternally separated animals from parvalbumin loss in adolescence. Linear regression analyses revealed that increased circulating levels of the pro-inflammatory cytokines IL-1 and IL-6 predicted lowered parvalbumin levels in maternally separated adolescents. Maternal separation also increases cortical expression of the NR2A NMDA receptor subunit in adolescence, which is prevented by IL-10 treatment. These data suggest that inflammatory damage to parvalbumin interneurons may occur via aberrant glutamatergic activity in the prefrontal cortex. Our findings provide a novel interactive mechanism between inflammation and neural dysfunction that helps explain deleterious effects of early life adversity on prefrontal cortex interneurons.
    Brain Behavior and Immunity 11/2012; 28. DOI:10.1016/j.bbi.2012.11.012 · 5.89 Impact Factor
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